Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma.
Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a prior...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat de Lleida (UdL) |
| Repositorio: | Repositori Obert UdL |
| OAI Identifier: | oai:repositori.udl.cat:10459.1/83786 |
| Acceso en línea: | https://doi.org/10.3390/ijms23158199 http://hdl.handle.net/10459.1/83786 |
| Access Level: | acceso abierto |
| Palabra clave: | Glioma Glioblastoma Ral-GTPases RalB Recurrence Therapy |
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Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma.Cemeli, TàniaGuasch Vallés, MartaRibes Santolaria, MarinaIbars Estiarte, Eva IreneNavaridas Fernández de Bobadilla, RaúlDolcet Roca, XavierPedraza González, NeusColomina i Gabarrella, NeusTorres Rosell, JordiFerrezuelo, FranciscoHerreros Danés, JuditGarí Marsol, EloiGliomaGlioblastomaRal-GTPasesRalBRecurrenceTherapyGlioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.This work was funded by the Catalan Government—AGAUR (2017 SGR-569), Ministerio de Ciencia e Innovaciön (PID2019-104859GB-I00; RTI2018-094739-B-I00; PID2019-104734RB-I00), and by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncologia de Catalunya (XBTC). T Cemeli (FPU13/06590), M.Guasch (FPU17/00229), R. Navaridas (FPU18/04480), and M. Ribes (TALENT-IRBLleida) were supported by a pre-doctoral fellowship from Ministerio de Educación, Cultura y Deportes, and from Diputació de Lleida.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.3390/ijms23158199http://hdl.handle.net/10459.1/83786reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)Inglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104859GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094739-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104734RB-I00Reproducció del document publicat a: https://doi.org/10.3390/ijms23158199International Journal Of Molecular Sciences, 2022, vol. 23, núm. 15, p. 8199cc-by (c) Cemeli, Tània et al., 2022info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/837862026-06-24T12:42:17Z |
| dc.title.none.fl_str_mv |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| title |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| spellingShingle |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. Cemeli, Tània Glioma Glioblastoma Ral-GTPases RalB Recurrence Therapy |
| title_short |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| title_full |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| title_fullStr |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| title_full_unstemmed |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| title_sort |
Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma. |
| dc.creator.none.fl_str_mv |
Cemeli, Tània Guasch Vallés, Marta Ribes Santolaria, Marina Ibars Estiarte, Eva Irene Navaridas Fernández de Bobadilla, Raúl Dolcet Roca, Xavier Pedraza González, Neus Colomina i Gabarrella, Neus Torres Rosell, Jordi Ferrezuelo, Francisco Herreros Danés, Judit Garí Marsol, Eloi |
| author |
Cemeli, Tània |
| author_facet |
Cemeli, Tània Guasch Vallés, Marta Ribes Santolaria, Marina Ibars Estiarte, Eva Irene Navaridas Fernández de Bobadilla, Raúl Dolcet Roca, Xavier Pedraza González, Neus Colomina i Gabarrella, Neus Torres Rosell, Jordi Ferrezuelo, Francisco Herreros Danés, Judit Garí Marsol, Eloi |
| author_role |
author |
| author2 |
Guasch Vallés, Marta Ribes Santolaria, Marina Ibars Estiarte, Eva Irene Navaridas Fernández de Bobadilla, Raúl Dolcet Roca, Xavier Pedraza González, Neus Colomina i Gabarrella, Neus Torres Rosell, Jordi Ferrezuelo, Francisco Herreros Danés, Judit Garí Marsol, Eloi |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Glioma Glioblastoma Ral-GTPases RalB Recurrence Therapy |
| topic |
Glioma Glioblastoma Ral-GTPases RalB Recurrence Therapy |
| description |
Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://doi.org/10.3390/ijms23158199 http://hdl.handle.net/10459.1/83786 |
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https://doi.org/10.3390/ijms23158199 http://hdl.handle.net/10459.1/83786 |
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Inglés |
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Inglés |
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104859GB-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094739-B-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104734RB-I00 Reproducció del document publicat a: https://doi.org/10.3390/ijms23158199 International Journal Of Molecular Sciences, 2022, vol. 23, núm. 15, p. 8199 |
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cc-by (c) Cemeli, Tània et al., 2022 info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/4.0/ |
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cc-by (c) Cemeli, Tània et al., 2022 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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MDPI |
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MDPI |
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